Unveiling the seroprevalence of human papillomavirus in Guangdong, China: Implications for vaccination strategies.

Seroepidemiological characteristics of human papillomavirus (HPV) in community residents reflect natural infection and can guide the reform of vaccination programs. A population-based serological survey was conducted in Guangdong Province. Serum anti-HPV IgG antibody levels were determined by an ELISA. Neutralizing antibodies against HPV6, 11, 16, and 18 were detected via a pseudovirus-based neutralization assay (PBNA). A total of 5122 serum samples were collected from community residents, including 1989 males and 3133 females, in three cities of Guangdong Province. The rate of HPV IgG antibody positivity in females was 5.39% (95% CI: 4.6-6.2), which was greater than that in males (2.36%; 95% CI: 1.7-3.1). HPV IgG antibodies were more frequently detected in females aged 51-60 years (11.30%; 95% CI: 7.6-16.0), whereas in males, the detection increased with age and reached 4.94% (95% CI: 2.8-6.9) in the group aged ≥71 years. The seropositivity of neutralizing antibodies against HPV6 and 11 was greater than that against HPV16 and 18. The serum neutralizing antibody titers in individuals who received three doses of a vaccine were 7- to 12-fold greater than those in individuals who did not receive the vaccine. The neutralizing antibody titers slightly decreased within 40 months and ranged from 0.038 to 0.057 log ED50 per month. A moderate consistency between the HPV ELISA and PBNA results was observed (Kappa score = 0.49, r = 0.249, 0.635, 0.382, and 0.466 for HPV6, 11, 16, and 18, respectively). The HPV seropositivity rate among healthy residents of Guangdong Province was found to be low among children and adolescents and to increase with age. The serum neutralizing antibody titers were significantly greater in the vaccine group than that in the control group, and this difference persisted over time, which indicated promising protection against HPV infection.

Chloroplast ATP synthase restricts photosynthesis under fluctuating light in tomato but not in maize.

Photosynthesis in fluctuating light requires coordinated adjustments of diffusion conductance and biochemical capacity, but the role of chloroplast ATP synthase activity (gH+) in dynamic photosynthesis is not well understood. In this study, we measured gas exchange, chlorophyll fluorescence and electrochromic shift signals in fluctuating light for leaves of tomato (Solanum lycopersicum) and maize (Zea mays). During the transition from sun to shade, simultaneous increases in gH+, effective quantum yield of PSII, and net CO2 assimilation rate (AN) occurred in tomato but uncoupled in maize, indicating that gH + limited AN during the sun-to-shade transition in tomato but not in maize. During the shade-to-sun transition, gH + increased simultaneously with stomatal conductance, mesophyll conductance and Rubisco carboxylation capacity in tomato, suggesting that gH+ is an overlooked factor affecting light induction of AN in tomato. By comparison, gH + maintained at high levels in maize and its AN was mainly restricted by stomatal conductance. Our results reveal that the kinetics of gH+ in fluctuating light differs between species, and chloroplast ATP synthase may be a potential target for improving dynamic photosynthesis in crops such as tomato.

Calotropin attenuates ischemic heart failure after myocardial infarction by modulating SIRT1/FOXD3/SERCA2a pathway.

Heart failure (HF) represents the terminal stage of cardiovascular diseases, with limited therapeutic options currently available. Calotropin (CAL), a cardenolide isolated from Calotropis gigantea, exhibits a similar chemical structure and inhibitory effect on Na+/K+-ATPase to digoxin, a positive inotropic drugs used in heart failure treatment. However, the specific effect of calotropin in ischemic HF (IHF) remains unknown. The objective of this study is to assess the anti-HF effect and clarify its underlying mechanisms. The left anterior descending (LAD) artery ligation on Male Sprague-Dawley (SD) rats was used to construct ischemic HF model. Daily administration of CAL at 0.05 mg/kg significantly enhanced ejection fraction (EF) and fractional shortening (FS), while inhibiting cardiac fibrosis in IHF rats. CAL reduced the OGD/R-induced H9c2 cell injury. Furthermore, CAL upregulated the expression of SERCA2a and SIRT1. The cardioprotective effect of CAL against IHF was abrogated in the presence of the SIRT1 inhibitor EX527. Notably, we identified FOXD3 as a pivotal transcription factor mediating CAL-induced SERCA2a regulation. CAL promoted the deacetylation and nuclear translocation of FOXD3 in a SIRT1-dependent manner. In conclusion, our study explores a novel mechanism of calotropin for improving cardiac dysfunction in ischemic heart failure by regulating SIRT1/FOXD3/SERCA2a pathway.

Efficient and fast arsenate removal from water by in-situ formed magnesium hydroxide.

MgO nanoparticles have good As-adsorption capacity in treating As-contaminated wastewater but suffer from high production cost. In this study, instead of using pre-formed MgO nanoparticles, we found that in-situ formed Mg(OH)2 from MgCl2 and NaOH reaction exhibited super high arsenate (As(V)) removal efficiency. Only 1.5 mmol/L of in-situ formed Mg(OH)2 could remove more than 95% As(V) within 10 min to make the As contaminated water (10 mg-As(V)/L) meet the municipal wastewater treatment standard, whereas MgO nanoparticles failed. The Mg-As sludge has an amorphous crystal structure while no Mg(OH)2 phase could be observed. As(V) existed uniformly within the sludge which was confirmed by elemental mapping. A precipitation-adsorption-coagulation mechanism might exist, which could relieve the restriction of limited surface area of solid MgO adsorbents. This study not only reveals an applicable method for efficient removal of trace level As(V) from water but also implies the huge potential of in-situ formed adsorbents in water treatment.

Microplastics caused embryonic growth retardation and placental dysfunction in pregnant mice by activating GRP78/IRE1α/JNK axis induced apoptosis and endoplasmic reticulum stress.

Microplastics (MPs), a brand-new class of worldwide environmental pollutant, have received a lot of attention. MPs are consumed by both humans and animals through water, food chain and other ways, which may cause potential health risks. However, the effects of MPs on embryonic development, especially placental function, and its related mechanisms still need to be further studied. We investigated the impact on fetal development and placental physiological function of pregnant mice by consecutive gavages of MPs at 0, 25, 50, 100 mg/kg body weight during gestational days (GDs 0-14). The results showed that continuous exposure to high concentrations of MP significantly reduced daily weight gain and impaired reproductive performance of pregnant mice. In addition, MPs could significantly induce oxidative stress and placental dysfunction in pregnant mice. On the other hand, MPs exposure significantly decreased placental barrier function and induced placental inflammation. Specifically, MPs treatment significantly reduced the expression of tight junction proteins in placentas, accompanied by inflammatory cell infiltration and increased mRNA levels of pro-inflammatory cytokines and chemokines in placentas. Finally, we found that MPs induced placental apoptosis and endoplasmic reticulum (ER) stress through the GRP78/IRE1α/JNK axis, leading to placental dysfunction and decreased reproductive performance in pregnant mice. We revealed for the first time that the effects of MPs on placental dysfunction in pregnant animals. Blocking the targets of MPs mediated ER stress will provide potential therapeutic ideas for the toxic effects of MPs on maternal pregnancy.

Molecular designing of potential environmentally friendly PFAS based on deep learning and generative models.

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are widely used across a spectrum of industrial and consumer goods. Nonetheless, their persistent nature and tendency to accumulate in biological systems pose substantial environmental and health threats. Consequently, striking a balance between maximizing product efficiency and minimizing environmental and health risks by tailoring the molecular structure of PFAS has become a pivotal challenge in the fields of environmental chemistry and sustainable development. To address this issue, a computational workflow was proposed for designing an environmentally friendly PFAS by incorporating deep learning (DL) and molecular generative models. The hybrid DL architecture MolHGT+ based on heterogeneous graph neural network with transformer-like attention was applied to predict the surface tension, bioaccumulation, and hepatotoxicity of the molecules. Through virtual screening of the PFAS master database using MolHGT+, the findings indicate that incorporating the siloxane group and betaine fragment can effectively decrease both the bioaccumulation and hepatotoxicity of PFAS while preserving low surface tension. In addition, molecular generative models were employed to create a structurally diverse pool of novel PFASs with the aforementioned hit molecules serving as the initial template structures. Overall, our study presents a promising AI-driven method for advancing the development of environmentally friendly PFAS.

Promoting starch interaction with genistein to slow starch digestion using an antisolvent method.

Genistein could interact with starch to slow starch digestion by forming starch-genistein complexes. However, genistein had low solubility in water, which hindered the interaction with starch and therefore the formation of the complexes. This study presented a pathway to promote the formation of starch-genistein complexes using an antisolvent method in two steps: (i) adding ethanol to the solution containing starch and genistein to increase genistein solubility, and (ii) evaporating ethanol from the solution to promote genistein interaction with starch. The complexes prepared using this antisolvent method had higher crystallinity (9.45 %), complex index (18.17 %), and higher content of resistant starch (RS) (19.04 %) compared to samples prepared in pure water or ethanol-containing aqueous solution without ethanol evaporation treatment (these samples showed crystallinity of 6.97 %-8.00 %, complex index of 9.09 %-11.4 2%, and RS of 4.45 %-14.38 %). Molecular dynamic simulation results confirmed that the changes in solution polarity significantly determined the formation of starch-genistein complexes. Findings offered a feasible pathway to efficiently promote starch interaction with genistein and in turn mitigate starch digestibility.

Comparison of Cytomegalovirus Reactivation in Children After Allogeneic Hematopoietic Cell Transplantation in 2 Transplant Eras.

BACKGROUND: Reactivation of cytomegalovirus (CMV) is typically considered harmless as long as the immune system remains unaffected by medications or other factors. CMV reactivation may occur as a result of acute graft-versus-host disease of Grades II to IV. One possible factor contributing to this risk is the rise in the number of donors who lack genetic similarities or relationships. We hypothesized that the anti-CMV IgG level before transplantation could potentially serve as an indicator of the likelihood of CMV reactivation following hematopoietic cell transplantation. METHODS: We examined a cohort of young individuals who underwent allogeneic HCT between 1998 and 2022 to evaluate the occurrence of CMV reactivation. The patients were divided into 2 time periods: 1998 to 2016 (comparison group) and 2017 to 2022 (intervention group). RESULTS: Between 1998 and 2016, 292 patients underwent hematopoietic HCT. Recipients from 2017 to 2022 experienced a slightly higher risk of CMV reactivation than those from 1998 to 2016. The comparison of prophylactic and preemptive medication showed no significant difference between the periods (P = .32). Patients treated from 1998 to 2016 experienced a 23% decrease in the risk of symptomatic CMV reactivation and related illnesses compared to those treated from 2017 to 2022 (P = .08 and .15, respectively). CONCLUSIONS: Our study showed that the intervention group had more symptomatic CMV reactivations. Various factors may contribute to this, including CD19-directed immunotherapy and the CMV status of the recipient before transplantation.

The gut microbiota improves reproductive dysfunction in obese mice by suppressing the NLRP3/ASC/caspase-1 axis.

Aim: To explore the complex relationship between gut microbiota, obesity-related male reproductive impairments, and the NLRP3 inflammasome.Methods: A high-fat diet was administered to induce obesity in a mouse model, fecal microbiota transplantation or a high-dietary fiber diet (HDFD) was administered for 5 weeks to evaluate changes in parameters related to reproductive capacity, NLRP3, gut microbiota composition and metabolites in mice.Results: A high-fat diet induces obesity and decreases reproductive capacity in male mice. Fecal microbiota transplantation and HDFD can improve reproductive capacity in obese mice by adjusting the gut microbiota population to suppress the NLRP3/ASC/caspase-1 axis, thereby reducing IL-1ß levels.Conclusion: This study offers a potential treatment for obesity-induced reproductive dysfunction by targeting the gut microbiota and the NLRP3 inflammasome pathway.

This study looks at how gut bacteria, obesity and our immune system affect male reproductive health. We made mice obese by feeding them a high-fat diet. Then, we treated them with either a transplant of gut bacteria or a high-fiber diet for 5 weeks. We found that the high-fat diet made it harder for male mice to have babies. Both the transplant and the high-fiber diet helped improve their ability to reproduce. Changing the bacteria in their gut reduced inflammation by affecting the immune system. Our findings suggest that changing gut bacteria and focusing on this part of the immune system could help with reproductive problems caused by obesity.

Perovskite-silicon tandem solar cells with bilayer interface passivation.

Two-terminal monolithic perovskite-silicon tandem solar cells demonstrate huge advantages in power conversion efficiency (PCE) compared to their respective single-junction counterparts1,2. However, suppressing interfacial recombination at the wide-bandgap perovskite/electron transport layer interface, without compromising its superior charge transport performance, remains a significant challenge for perovskite-silicon tandem cells3,4. By exploiting the nanoscale discretely distributed LiF ultrathin layer followed by an additional deposition of diammonium diiodide molecule, we have devised a bilayer intertwined passivation strategy that combines efficient electron extraction with further suppression of nonradiative recombination. We constructed perovskite-silicon tandem devices on double-side textured Czochralski (CZ)-based silicon heterojunction cell, which featured a mildly-textured front surface and a heavily-textured rear surface, leading to simultaneously enhanced photocurrent and uncompromised rear passivation. The resulting perovskite-silicon tandem achieved an independently certified stabilized PCE of 33.89%, accompanied by an impressive fill factor (FF) of 83.0% and an open-circuit voltage (Voc) of nearly 1.97 volts. To our knowledge, this represents the first reported certified efficiency of a two-junction tandem solar cell exceeding the single-junction Shockley-Queisser limit of 33.7%.

The distribution of the extrachromosomal DNA molecules in early lung cancer.

Lung cancer (LC) is a highly lethal cancer worldwide. Research on the distribution and nature of extrachromosomal DNA molecules (EcDNAm) in early LC is scarce. In this study, after removing linear DNA and mitochondrial circular DNA, EcDNAm were extracted from two paired LC tissue samples and amplified using rolling circle amplification. High throughput extrachromosomal DNA (EcDNA) or RNA sequencing and bioinformatics analysis were subsequently utilized to explore the distribution and nature of the EcDNAm. Additionally, to elucidate the role of oncogenes with large EcDNAm sizes, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. The RNA sequencing results revealed significant differences in certain genes between tumors and corresponding normal samples. At the same time, slight distinctions were observed between relapsed and non-relapsed tumor samples. The nature of the EcDNAm was compared between LC samples and matched normal samples. There was a tendency for the number of EcDNAm with longer size (EcDNA) and its containing driver oncogenes to be higher in cancer samples. Enrichment analysis of the cancer samples revealed enrichment in biological processes, such as positive regulation of protein localization, axon development, and in-utero embryonic development. This study highlights the universal distribution and characteristics of EcDNAm in early LC. Moreover, our work fills the investigation of the EcDNAm gap and future studies should focus on the application of EcDNA as a potential biomarker in patients with early LC.

A case report of human infection with avian influenza H10N3 with a complex respiratory disease history.

BACKGROUND: On March 16th 2024, the first case of Human infection with avian influenza H10N3 since the end of the global COVID-19 Pandemic was reported in Kunming, China. To enhance comprehension of the source of infection and risk factors of the H10N3 virus infection, this case report summarizes the clinical features, epidemiological investigation, and laboratory test results. Provides recommendations for the prevention and control of Human infection with avian influenza H10N3. CASE PRESENTATION: A 51-year-old male with a history of COVID-19 infection and a smoking habit of 30 years, worked in livestock breeding and was exposed to sick and dead poultry before falling ill with fever and chills on 28th February 2024. A week later, he was diagnosed with severe pneumonia, influenza, and respiratory failure by the Third People's Hospital of Kunming(KM-TPH). He was discharged on 17th April and none of his 6 close contacts showed any symptoms of illness. Environmental samples taken from the epidemic spot revealed that peacock feces tested positive for avian influenza sub-type H9 and waterfowl specimens showed positive results for avian influenza sub-type H5. Gene sequencing conducted on positive specimens from the patient's respiratory tract by the Chinese Centre for Disease Control and Prevention (CCDC) showed a high degree of similarity (98.6-99.5%) with the strain responsible for the second global case of human infected with H10N3 (reported from Zhejiang, China 2022). CONCLUSIONS: According to the available epidemiological information, there is limited evidence to suggest that H10N3 viruses are excessively lethal. However, adaptive site mutations have been observed in the H10N3 isoform of mammals. While it is unlikely that the H10N3 virus will spread among humans, the possibility of additional cases cannot be entirely ruled out. Symptoms of human infection with H10N3 avian influenza are similar to those of common respiratory infections, which may result in them being overlooked during initial clinical consultations. Therefore, it is essential to improve surveillance of the H10 sub-type of avian influenza and to increase the awareness of hospital-related workers of cases of pneumonia of unknown origin.

Long-Term Exposure to Polystyrene Microspheres and High-Fat Diet-Induced Obesity in Mice: Evaluating a Role for Microbiota Dysbiosis.

BACKGROUND: Microplastics (MPs) have become a global environmental problem, emerging as contaminants with potentially alarming consequences. However, long-term exposure to polystyrene microspheres (PS-MS) and its effects on diet-induced obesity are not yet fully understood. OBJECTIVES: We aimed to investigate the effect of PS-MS exposure on high-fat diet (HFD)-induced obesity and underlying mechanisms. METHODS: In the present study, C57BL/6J mice were fed a normal diet (ND) or a HFD in the absence or presence of PS-MS via oral administration for 8 wk. Antibiotic depletion of the microbiota and fecal microbiota transplantation (FMT) were performed to assess the influence of PS-MS on intestinal microbial ecology. We performed 16S rRNA sequencing to dissect microbial discrepancies and investigated the dysbiosis-associated intestinal integrity and inflammation in serum. RESULTS: Compared with HFD mice, mice fed the HFD with PS-MS exhibited higher body weight, liver weight, metabolic dysfunction-associated steatotic liver disease (MASLD) activity scores, and mass of white adipose tissue, as well as higher blood glucose and serum lipid concentrations. Furthermore, 16S rRNA sequencing of the fecal microbiota revealed that mice fed the HFD with PS-MS had greater α-diversity and greater relative abundances of Lachnospiraceae, Oscillospiraceae, Bacteroidaceae, Akkermansiaceae, Marinifilaceae, Deferribacteres, and Desulfovibrio, but lower relative abundances of Atopobiaceae, Bifidobacterium, and Parabacteroides. Mice fed the HFD with PS-MS exhibited lower expression of MUC2 mucin and higher levels of lipopolysaccharide and inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß, and IL-17A] in serum. Correlation analyses revealed that differences in the microbial flora of mice exposed to PS-MS were associated with obesity. Interestingly, microbiota-depleted mice did not show the same PS-MS-associated differences in Muc2 and Tjp1 expression in the distal colon, expression of inflammatory cytokines in serum, or obesity outcomes between HFD and HFD + PS-MS. Importantly, transplantation of feces from HFD + PS-MS mice to microbiota-depleted HFD-fed mice resulted in a lower expression of mucus proteins, higher expression of inflammatory cytokines, and obesity outcomes, similar to the findings in HFD + PS-MS mice. CONCLUSIONS: Our findings provide a new gut microbiota-driven mechanism for PS-MS-induced obesity in HFD-fed mice, suggesting the need to reevaluate the adverse health effects of MPs commonly found in daily life, particularly in susceptible populations. https://doi.org/10.1289/EHP13913.

Hydrothermal synthesis, structures, and catalytic performance of five coordination compounds driven by 5-aminoisophthalic acid.

An amino-functionalized-dicarboxylic acid, 5-aminoisophthalic acid (H2aipa), was used as a versatile building block to synthesize a series of five novel coordination compounds under hydrothermal conditions and formulated as [Co(µ3-aipa)(2,2'-H2biim)] n (1), [Ni2(µ-aipa)2(2,2'-H2biim)2(H2O)4]·4H2O (2), {[Cd(µ3-aipa)(2,2'-H2biim)]·H2O} n (3), {[Ni(µ-aipa)(µ-bpb)]·0.5bpb·H2O} n (4), and {[Ni2(µ-aipa)(µ3-aipa)(µ-dpea)2(H2O)][Ni(µ-aipa)(µ-dpea)(H2O)]·8H2O} n (5). Three supporting ligands (2,2'-biimidazole (H2biim),1,4-bis(pyrid-4-yl)benzene (bpb), and 1,2-di(4-pyridyl)ethane (dpea)) were used in the synthesis. The structures of the studied products 1-5 vary significantly, ranging from a 0D dimer (2), 2D sheets (1, 3 and 4) to 3D + 2D interpenetrated frameworks (5). Furthermore, these compounds were evaluated as heterogeneous catalysts for the Knoevenagel reaction, achieving high product yields under optimized conditions. In addition, we also investigated various reaction parameters, substrate scope, and assessed the feasibility of catalyst recycling. This thorough investigation highlights the versatility of H2aipa as a dicarboxylate building block in the formation of functional coordination polymers.

A cuproptosis-related prognostic signature for guiding clinical diagnosis and treatment in uveal melanoma patients.

Background: Cuproptosis, one of the most recently discovered forms of cell death, is induced by the disruption of copper binding to the mitochondrial respiratory acylation components. However, the mechanism underlying cuproptosis in uveal melanoma (UM) has not yet been adequately studied. Methods: RNA and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed cuproptosis-related genes were identified by R software. A prognostic signature was constructed by applying LASSO regression and Cox regression models. The associations between the signature and the immune microenvironment, overall survival, and drug sensitivity were studied. In addition, qPCR and Western blotting were performed on UM cells and RPE cell lines to verify the expression levels of the genes encoding dihydrolipoamide dehydrogenase (DLD) and dihydrolipoamide S-succinyltransferase (DLST) in UM cases. Results: Using a cuproptosis-related prognostic signature, UM samples were classified into high- and low-risk groups. A significant difference in overall survival between the two risk groups was evident. Receiver operating characteristic curves demonstrated that the signature is a reliable predictor of prognosis. Immune cell infiltration, drug sensitivity, and immune checkpoint expression were analysed. Significant immune difference between the two high-risk groups was found, and the high expression of immune checkpoints in high-risk groups suggests significant immunotherapy potential. In addition, drug sensitivity analysis experiments suggest that erlotinib may be a potential treatment for high-risk patients. The results of in vitro experiments confirmed that DLD and DLST had higher expression levels in UM cell lines. Conclusions: The prognostic signature developed in this study is a reliable biomarker for predicting the prognosis of UM and may serve as a tool for personalised treatment of patients with UM.

Comparison of rotational stability of the Implantable Collamer Lens after using a vertical or horizontal implanting orientation.

PURPOSE: To compare rotational stability of the Implantable Collamer Lens (ICL) between horizontal and vertical implantation. SETTING: Zhongshan Ophthalmic Center, China. DESIGN: Prospective 1:1 matched design. METHODS: 94 cases (185 eyes with a vertical elliptical ciliary sulcus) were included with a 1:1 matched design based on ciliary sulcus morphology, preset deviation angle, and vault. Follow-ups at 4 days, 1 month, 3 months, and 6 months post-surgery measured rotational angles using slit-lamp photography. Latent class trajectory modeling was employed to investigate the postoperative rotational angle trajectories. RESULTS: Six months after surgery, both groups exhibited similar visual acuity and refractive outcomes. The horizontal group had a significantly greater rotation angle than the vertical group (F group = 13.638, P < 0.001). Additionally, a statistically significant difference (P = 0.004) in the average trajectories of rotational angles was observed. The vertical group displayed a greater presence in the low-stable trajectory subgroup while demonstrating a reduced presence in the moderate-increase and high-fluctuation trajectory subgroups compared to the horizontal group. The horizontal group had a 3.750 times higher risk of rotation angle ≥3° compared to the vertical group, which represented a statistically significant difference (95% CI: 1.346∼10.446). In both groups, a positive correlation between the preset deviation angle and the rotation angle was observed, with correlation coefficients of 0.320 (P = 0.030) and 0.371 (P = 0.011), respectively. CONCLUSIONS: Vertical ICL implantation showed better rotational stability than horizontal implantation in eyes with a vertical elliptical ciliary sulcus, offering guidance for ICL surgery.

Radiomics nomogram for predicting chemo-immunotherapy efficiency in advanced non-small cell lung cancer.

This study aimed to explore potential radiomics biomarkers in predicting the efficiency of chemo-immunotherapy in patients with advanced non-small cell lung cancer (NSCLC). Eligible patients were prospectively assigned to receive chemo-immunotherapy, and were divided into a primary cohort (n = 138) and an internal validation cohort (n = 58). Additionally, a separative dataset was used as an external validation cohort (n = 60). Radiomics signatures were extracted and selected from the primary tumor sites from chest CT images. A multivariate logistic regression analysis was conducted to identify the independent clinical predictors. Subsequently, a radiomics nomogram model for predicting the efficiency of chemo-immunotherapy was conducted by integrating the selected radiomics signatures and the independent clinical predictors. The receiver operating characteristic (ROC) curves demonstrated that the radiomics model, the clinical model, and the radiomics nomogram model achieved areas under the curve (AUCs) of 0.85 (95% confidence interval [CI] 0.78-0.92), 0.76 (95% CI 0.68-0.84), and 0.89 (95% CI 0.84-0.94), respectively, in the primary cohort. In the internal validation cohort, the corresponding AUCs were 0.93 (95% CI 0.86-1.00), 0.79 (95% CI 0.68-0.91), and 0.96 (95% CI 0.90-1.00) respectively. Moreover, in the external validation cohort, the AUCs were 0.84 (95% CI 0.72-0.96), 0.75 (95% CI 0.62-0.87), and 0.86 (95% CI 0.75-0.96), respectively. In conclusion, the radiomics nomogram provides a convenient model for predicting the effect of chemo-immunotherapy in advanced NSCLC patients.

Reprogramming macrophage metabolism following myocardial infarction: A neglected piece of a therapeutic opportunity.

Given the global prevalence of myocardial infarction (MI) as the leading cause of mortality, there is an urgent need to devise novel strategies that target reducing infarct size, accelerating cardiac tissue repair, and preventing detrimental left ventricular (LV) remodeling. Macrophages, as a predominant type of innate immune cells, undergo metabolic reprogramming following MI, resulting in alterations in function and phenotype that significantly impact the progression of MI size and LV remodeling. This article aimed to delineate the characteristics of macrophage metabolites during reprogramming in MI and elucidate their targets and functions in cardioprotection. Furthermore, we summarize the currently proposed regulatory mechanisms of macrophage metabolic reprogramming and identify the regulators derived from endogenous products and natural small molecules. Finally, we discussed the challenges of macrophage metabolic reprogramming in the treatment of MI, with the goal of inspiring further fundamental and clinical research into reprogramming macrophage metabolism and validating its potential therapeutic targets for MI.

Diabetic foot exacerbates gut mycobiome dysbiosis in adult patients with type 2 diabetes mellitus: revealing diagnostic markers.

Type 2 diabetes mellitus (T2DM) is globally recognized as a significant health concern, with diabetic foot (DF) identified as a severe long-term complication that can lead to tissue death or amputation. The discovery of the impact of mycobiota, a diverse group of multicellular eukaryotes in the gut microbiome, on the onset of endocrine disorders holds great significance. Therefore, this research aimed to examine variations in fungal mycobiome and identify potential biomarkers for T2DM and T2DM-DF. Fecal and blood samples were collected from 33 individuals with T2DM, 32 individuals with T2DM-DF, and 32 healthy individuals without any health conditions (HC). Blood samples were used for laboratory parameters analysis, while total DNA was extracted from fecal samples and sequenced using Illumina 18s rRNA. Bioinformatics tools were employed to analyze fungal abundance and diversity, revealing differentially expressed fungal species and signature fungi that distinguished between T2DM, T2DM-DF, and HC groups. Firstly, significant alterations in some laboratory parameters were observed among the three groups, which also differed between T2DM and T2DM-DF. The diversity of gut fungi in T2DM and T2DM-DF significantly differed from that of the HC group; however, more pronounced changes were observed in T2DM-DF. Additionally, two significantly altered phyla, Ascomycota and Basidiomycota, were identified with higher Ascomycota abundance but lower Basidiomycota abundance in both the T2DM and T2DM-DF compared to the HC group. Furthermore, the top 15 fungi showing significant changes at the species level included a notable decrease in Rhodotorula_mucilaginosa abundance in patients with T2DM compared to HC and a substantial increase in unclassified_g_Candida abundance specifically seen only among patients with T2DM-DF, but not among those diagnosed with T2DM or HC. Thirdly, KEGG was employed to analyze enzyme expression across the three groups, revealing a more pronounced alteration in gut fungal function within T2DM-DF compared to T2DM. Subsequently, to accurately identify signature fungi in each group, a random forest was utilized to rank the top 15 significant fungi. Notably, 11 fungi were identified as potential biomarkers for distinguishing T2DM or T2DM-DF from HC, while eight fungi could discriminate between T2DM and T2DM-DF. Furthermore, receiver operating characteristic curve (ROC) analysis demonstrated enhanced accuracy of predicted outcomes. These findings suggest that changes in fungal mycobiome are closely associated with the progression and complications of T2DM and DF, offering promising prospects for diagnosis and treatment.